Biodegradable microdepot delivery system for topical delivery

Abstract

The present invention provides a biodegradable microdepot delivery system for topical delivery of active ingredients through the skin surface of a subject. The configuration, dimension, and chemical composition of the microdepots allow a relatively short dissolution time of less than 5 minutes while insertion ratio of the microdepots can reach more than 60%, some of which can even reach about 97%, under exertion of a relatively low pressing force. The present invention also provides a method for fabricating the biodegradable microdepot delivery system and a polymeric solution for forming the same.

What is claimed is: 
     
       1. A polymeric solution for forming an array of microdepots of a biodegradable microdepot delivery system, said polymeric solution comprising one or more biodegradable polymers, a glycosaminoglycan, and a polysaccharide, the weight ratio of glycosaminoglycan:polysaccharide:biodegradable polymer is 9-11:10-8:1; said one or more biodegradable polymers is Povidone K90; said polysaccharide is dextran 70; said glycosaminoglycan is hyaluronic acid and wherein the total concentration of Povidone K90, dextran 70 and hyaluronic acid is 50% by volume of the polymeric solution. 
     
     
       2. The solution of  claim 1 , wherein the glycosaminoglycan of the polymeric solution is hyaluronic acid (HA) ranging from 22.5-27.5% v/v. 
     
     
       3. The solution of  claim 1 , wherein the polysaccharide of the polymeric solution is dextran 70 ranging from 20-25% v/v. 
     
     
       4. The solution of  claim 1 , further comprising sodium carboxymethyl cellulose (CMC) ranging from 5 to 30% v/v. 
     
     
       5. The solution of  claim 1 , further comprising one or more active ingredients comprising amides and peptides. 
     
     
       6. The solution of  claim 5 , wherein the one or more active ingredients comprise 2% w/v Niacinamide, 3-10% w/v Pal-KTTKS, and/or 0.2-5% w/v GHK-Cu. 
     
     
       7. The solution of  claim 1 , wherein the weight ratio of glycosaminoglycan:polysaccharide:biodegradable polymer is 9:10:1. 
     
     
       8. A biodegradable microdepot delivery system for topical delivery of active ingredients comprising an array of microdepots formed by the polymeric solution of  claim 1  and a base supporting said array, each microdepot having an aseptic ratio from 1 to 10, a height from 300 to 600 μm and a base width from 150 to 300 μm, each microdepot being either cone-shaped, pyramid-shaped or bevel-angled, the array being degraded within 60 minutes after being exposed to a skin surface using a force of as low as 0.3N and having an insertion efficiency of more than 60%. 
     
     
       9. The system of  claim 8 , wherein said array has one hundred microdepots on the surface opposite to the base in a configuration of 10×10 microdepots in a surface area of 1 cm 2 . 
     
     
       10. The system of  claim 8 , wherein each microdepot of said array incorporates at least one active ingredient to be delivered to the skin surface. 
     
     
       11. The system of  claim 8 , wherein a tip-to-tip distance between two microdepots is from 500 to 600 μm. 
     
     
       12. The system of  claim 8 , wherein the aseptic ratio is between 2 and 3. 
     
     
       13. The system of  claim 10 , wherein said at least one active ingredient comprises amides and peptides. 
     
     
       14. The system of  claim 10 , wherein said at least one active ingredient comprises Niacinamide, Pal-KTTKS and GHK-Cu. 
     
     
       15. The system of  claim 8 , wherein said base has a thickness of about 100 μm. 
     
     
       16. A method for fabricating the biodegradable microdepot delivery system of  claim 8 , said method comprising:
 (a) providing a mould for forming a microdepot template; 
 (b) forming a microdepot template corresponding to the mould and fixing the template at a centre of a centrifuge holder; 
 (c) adding a polymeric solution to one surface of the template for forming the biodegradable microdepot delivery system; 
 (d) centrifuging at a speed by a centrifuge for certain period of time at certain temperature such that the polymeric solution is centrifuged down to a plurality of wells on said surface of the template; 
 (e) repeating steps (c) and (d) for at least 4 times; and 
 (f) drying the template with the polymeric solution for at least 1 day to form the biodegradable microdepot delivery system. 
 
     
     
       17. The method of  claim 16 , wherein the number of wells to be formed on said surface of the microdepot template is 100 where each of the longitudinal and lateral axes of the template contains 10 wells. 
     
     
       18. The method of  claim 16 , wherein a tip-to-tip distance between two wells is from 500 to 600 μm. 
     
     
       19. The method of  claim 16 , wherein the microdepot template is in a form of an array with a surface area of 1 cm 2 . 
     
     
       20. The method of  claim 16 , wherein the volume of the polymeric solution to be added to one surface of the microdepot template is from 100 to 200 μl each time. 
     
     
       21. The method of  claim 16 , wherein the centrifuge is set at a speed from 4,500 to 7,500 rpm for 10 to 60 minutes at a temperature from 20° C. to 30° C. to centrifuge the polymeric solution added to said surface of the microdeport template. 
     
     
       22. The method of  claim 21 , wherein the speed of the centrifuge is set at 4,680 rpm. 
     
     
       23. The method of  claim 21 , wherein the time for centrifugation is for 30 minutes. 
     
     
       24. The method of  claim 21 , wherein the temperature during centrifugation is 25° C. 
     
     
       25. The method of  claim 16 , wherein steps (c) and (d) are repeated for 4 to 6 times until all the wells of the template are filled up with the polymeric solution and a thin layer of the polymeric solution covers said surface of the template. 
     
     
       26. The method of  claim 16 , wherein said drying is for 1 to 4 days. 
     
     
       27. The method of  claim 16 , wherein one or more active ingredients comprising 2% w/v Niacinamide, 3-10% w/v Pal-KTTKS, and/or 0.2-5% w/v GHK-Cu are mixed with the polymeric solution before said adding the polymeric solution to one surface of the template for forming the biodegradable microdepot delivery system in step (c).